Malignant hyperthermia

Question 1

Define malignant hyperthermia

Answer 1

Inherited myopathy characterized by a hypermetabolic state and muscle rigidity. Susceptible patients once exposed to certain triggering agents develop a sustained increase in temperature and associated complications

Question 2

What is the mortality of malignant hyperthermia

Answer 2

Was > 10% fallen to 2 - 10 % in recent years due to greater awareness and training

Question 3

What is the inheritance of malignant hyperthermia

Answer 3

Autosomal dominant with variable penetrance –> 50% of children with susceptible parents are potentially at risk

Question 4

Describe the genetic aetiology of MH

Answer 4

Mutation on the ryanodine receptor gene (RYRI) on chromosome 19q (30 -80% of families)

The ryanodine receptor gene encodes the skeletal muscle sarcoplasmic reticulum calcium release channel. The mutation impairs calcium re-uptake by the SR which leads to sustained muscle contraction and a hypermetabolic state

Question 5

How does the increased intracellular calcium in malignant hyperthermia lead to a hypermetabolic state

Answer 5

Directly activates phosphorylase to increase glycolysis and

Indirectly because of increased demand for ATP production (needed for calcium sequestration)

Question 6

What are the possible associated with MH

Answer 6

Strong associations
- Central core disease

Possible associates

• Patients with a tendency for heat stroke
• Strabismus

Question 7

List possible MH precipitants relevant to anaesthetics

Answer 7

1. All volatile anaesthetic agents

2. Succinylcholine

Question 8

What are the early signs of malignant hyperthermia?

Answer 8

Sustained jaw rigidity after SUX
- may persist for several minutes at a time when relaxation would be expected

Respiratory

• Tachypnoea with increased Ve
• Increasing ETCO2

CVS

• Tachycardia
• Ventricular ectopics
• Peaked T-waves - hyperkalaemia

Question 9

What are the intermediate signs and symptoms of MH

Answer 9

Increasing Temperature
Desaturation
Arrhythmia

ABG:

• Mixed resp/met acidosis
• Hyperkalaemia
• Hypercalcaemia
• Raised serum CK (rhabdomyolysis

Question 10

What are the LATE signs and symptoms of MH

Answer 10

Generalized muscle rigidity
Difficult ventilation (chest wall rigidity)
Arrhythmias - severe
Oliguria
Myoglobinuria
Prolonged bleeding time
Death

Question 11

What conditions might mimic the clinical presentation of malignant hyperthermia

Answer 11

A.	Inadequate anaesthesia/analgesia			 
B.	Inappropriate fresh gas flow/ventilation			 
C.	Infection/sepsis				 
D.	Tourniquet ischaemia			 
E.	Anaphylaxis			 
F.	Phaeochromocytoma		 
G.	Thyroid storm

Question 12

Summarize the treatment of malignant hyperthermia

Answer 12

1. HELP
2. Remove triggering agents
3. Dantrolene
4. Active cooling
5. Supportive
6. Teamwork

Question 13

In the management of MH, how are triggering agents removed

Answer 13

Do not administer suxamethonium
Turn of all vaporizers and change to 100% O2
Use a new clean breathing circuit with high FGF
Avoid sodalime
Maintain anaesthesia with intravenous agents (propofol)

Essentially: change to a new Bains breathing circuit with high FGF, stop volatile, switch to TIVA and give dantrolene

Question 14

Describe the presentation of dantrolene sodium

Answer 14

70 ml glass vial
Contains
- 20 mg dantrolene sodium
- 3 g mannitol and NaOH

Diluted with 60 ml H20 –> pH 9.5

Question 15

How long does dantrolene take to reconstitute

Answer 15

up to 20 minutes to dissolve – therefore start reconstitution asap

Question 16

What is the mode of action of dantrolene

Answer 16

Binds to the ryanodine receptor and interferes with release of calcium ions from the sarcoplasmic reticulum. Re-establishes myoplasmic calcium equilibrium

Question 17

What is the dose of dantrolene

Answer 17

Initial: 2.5 mg/kg

Subsequent boluses of 1 mg/kg to a maximum of 10mg/kg

Question 18

Describe methods used for active cooling

Answer 18

Cooled IV fluids
Convert active warming devices to active cooling devices
Ice packs in axillae
Cold gastric lavage
Cold peritoneal lavage
Cold bladder lavage
Extracorporeal heat exchange

Question 19

What should patients be referred for subsequent to recovering from an episode of malignant hyperthermia

Answer 19

In vitro contracture testing
- muscle biopsy exposed to halothane and caffeine
99% sensitive
93% specific

Consider genetic tests also and combine these to to establish a diagnosis

Question 20

Describe the general principles for administering an anaesthetic in a patient with previous episode of MH, diagnosis of MH or family hx of MH

Answer 20

No sux and no volatile
RA best
If GA required –> TIVA with NDNMB
Dantrolene at hand but prophylactic dantrolene not indicated
Use a vapour free anaesthetic machine (flush according to manufacturer guidelines

Question 21

How to create a ‘vapour free’ anaesthetic machine if one is not already available

Answer 21

Remove vaporizer
High flow O2 through machine, ventilator and bellows for 20 minutes
New soda lime
New breathing circuit, bag and masks